Context Valerian extract capsule (VEC) is an effective Chinese patent medicine used for gastrointestinal (GI) diseases. Objective To investigate the detailed pharmacological activity for VEC clinical effects in GI diseases. Materials and methods Sprague-Dawley rats were divided into six groups: control, model, and drug-treated (VEC-L, VEC-M, VEC-H, and teprenone). Rats were orally administered VEC (124, 248, 496 mg/kg) and teprenone (21.43 mg/kg) for 3 consecutive days. After 1 h, the five groups (except the control group) were orally given ethanol (10 mL/kg) for 1 h or indomethacin (80 mg/kg) for 7 h. The spasmolytic activity of VEC (0.01–1 mg/mL) on ACh/BaCl 2 -induced New Zealand rabbit smooth muscle contraction was performed. The C57BL/6 mice carbon propelling test evaluated the effects of VEC (248–992 mg/kg) on intestinal motility in normal and neostigmine/adrenaline-induced mice. Results Compared with the model group, VEC treatment reduced the gastric lesion index and mucosal damage. Further experiments showed that the pathological ameliorative effect of VEC was accompanied by augmentation of the enzymatic antioxidant system and cytoprotective marker (COX-1, p < 0.01; PGI2 p < 0.05;), along with the alleviation of the levels of MPO (ethanol: 15.56 ± 0.82 vs. 12.15 ± 2.60, p < 0.01; indomethacin: 9.65 ± 3.06 vs. 6.36 ± 2.43, p < 0.05), MDA (ethanol: 1.66 ± 0.44 vs. 0.81 ± 0.58, p < 0.01; indomethacin: 1.71 ± 0.87 vs. 1.09 ± 0.43, p < 0.05), and inflammatory mediators. VEC decreased the high tone induced by ACh/BaCl 2 and promoted intestinal transit in normal and neostigmine/adrenaline-induced mice. Discussion and conclusions VEC showed a potential gastroprotective effect, suggesting that VEC is a promising phytomedicine for the treatment of GI diseases.

Sinomenine (SIN) is a clinical drug for treating rheumatoid arthritis (RA) in China. Our previous study found SIN inhibited inflammation via alpha7 nicotinic acetylcholine receptor (α7nAChR) in macrophages in vitro. Adenosine receptor A2A has anti‐inflammatory and immunosuppressive function. However, the mechanisms of SIN acting on α7nAChR and the effect on adenosine A2A receptor (A2AR) in RA are not clear. In the present study, the effects of SIN on adjuvant‐induced‐arthritis (AIA) rats in vivo and on fibroblast‐like synoviocytes (FLSs) in vitro were investigated. Indomethacin (Indo) and methotrexate (MTX), the clinical anti‐arthritis drugs, were used as controls. Nicotine (Nic), a specific agonist of α7nAChR, was used as a control for targeting α7nAChR. Alpha‐bungarotoxin (α‐BTX), the antagonist of α7nAChR or small interference RNA (siRNA) was used to block or knock down α7nAChR. Results showed that SIN decreased arthritis index, hind paw volume, erythrocyte sedimentation (ESR) and serum TNF‐α in AIA rats, and α‐BTX attenuated the earlier‐mentioned effects of SIN and Nic, but not Indo and MTX. The expressions of A2AR in synovium declined in AIA rats, but remarkably increased after the intervention of SIN. The expression of A2AR decreased by LPS or TNF‐α, but increased by SIN; cAMP also increased by SIN in FLSs in vitro. SIN inhibited the expression of MCP‐1, IL‐6, and vascular endothelial growth factor in LPS‐induced FLSs. SIN inhibited the activation of NF‐κB. Meanwhile, α‐BTX or α7nAChR siRNA blocked the earlier‐mentioned effects of SIN in FLSs. Results suggested the expressions of A2AR in synovium and FLSs are negatively correlated with the arthritis progression of AIA rats and the activation of FLSs. SIN increases A2AR and inhibits the activation of NF‐κB pathway via α7nAChR in AIA rats and FLSs.

Background: Emerging evidence has suggested a pro-oncogenic role of calponin 1 (CNN1) in the initiation of a variety of cancers. Despite this, CNN1 remains unknown in terms of its effects and mechanisms on angiogenesis, prognosis, and immunology in cancer.Materials and Methods: The expression of CNN1 was extracted and analyzed using the TIMER, UALCAN, and GEPIA databases. Meanwhile, we analyzed the diagnostic value of CNN1 by using PrognoScan and Kaplan–Meier plots. To elucidate the value of CNN1 in immunotherapy, we used the TIMER 2.0 database, TISIDB database, and Sangerbox database. Gene set enrichment analysis (GSEA) was used to analyze the expression pattern and bio-progression of CNN1 and the vascular endothelium growth factor (VEGF) in cancer. The expressions of CNN1 and VEGF in gastric cancer were confirmed using immunohistochemistry. We used Cox regression analysis to investigate the association between pathological characteristics, clinical prognosis, and CNN1 and VEGF expressions in patients with gastric cancer.Results: CNN1 expression was higher in normal tissues than it was in tumor tissues of most types of cancers. However, the expression level rebounds during the development of tumors. High levels of CNN1 indicate a poor prognosis for 11 tumors, which include stomach adenocarcinoma (STAD). There is a relationship between CNN1 and tumor-infiltrating lymphocytes (TILs), and the marker genes NRP1 and TNFRSF14 of TILs are significantly related to CNN1 expression in gastric cancers. The GSEA results confirmed the lower expression of CNN1 in tumors when compared to normal tissues. However, CNN1 again showed an increasing trend during tumor development. In addition, the results also suggest that CNN1 is involved in angiogenesis. The immunohistochemistry results validated the GSEA result (take gastric cancer as an example). Cox analysis suggested that high CNN1 expression and high VEGF expression are closely associated with poor clinical prognosis.Conclusion: Our study has shown that CNN1 expression is aberrantly elevated in various cancers and positively correlates with angiogenesis and the immune checkpoint, contributing to cancer progression and poor prognosis. These results suggest that CNN1 could serve as a promising candidate for pan-cancer immunotherapy.